Catecholestrogens are synthesized by 2-hydroxylation in liver, brain and other organs and by demethylation in liver alone. The cytochrome P450 enzyme system is involved in all of these reactions. Breast tumors, but not normal breast tissue, can also synthesize and metabolize the catecholestrogens. In brain and liver, catecholestrogen synthesis is diminished in chronically hypothyroid rats and in castrated male rats. Phenobarbitol increases the synthesis in liver by demethylation only. Other cytochrome P450 dependent reactions occur in brain. P-hydroxyamphetamine, tyramine and octopamine are all converted to catecholamines, but phenolic narcotics are not metabolized to their catechol derivations in brain.